1. Field of the Invention
The present invention relates to mycology, entomology, and the use of preconidial preparations of entomopathogenic fungi as attractants (mycoattractants) and biopesticides (mycopesticides, mycoinsecticides) in combination with other technologies to control, decrease, limit or prevent the spread of diseases carried by insects and/or other arthropods. More particularly, the invention relates to the control of zoonotic diseases and plant diseases by attracting, or attracting and killing, insects, including ants, flies, beetles, cockroaches, bed bugs, mosquitoes, grasshoppers, flies and other arthropods such as ticks, mites, midges, lice and fleas, using pre-sporulating mycelia of entomopathogenic fungi and extracts of pre-sporulating mycelia.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Diseases emanating from ecologically distressed and polluted environments increasingly threaten animals and plants. With deforestation, habitat destruction, decline in water quality and decreases in biodiversity, all of which are exacerbated by global climate change and human impacts, zoonotic diseases are increasingly a threat to healthy environments and their inhabitants, especially animal populations, including humans and their livestock. Many of these disease-causing organisms are carried by or bred within insects or other arthropods. Insects are any of the large class (Insecta) of small arthropod animals characterized, in the adult state, by division of the body into head, thorax, and abdomen, three pairs of legs on the thorax, and, usually, two pairs of membranous wings; arthropods are any of the largest phylum (Arthropoda) of invertebrate animals with jointed legs, a segmented body, and an exoskeleton, including herein insects, arachnids such as spiders, mites and ticks, and myriapods. Since many of these bite humans and livestock, as well as damage plants, they transmit a wide variety of diseases, many of which result in billions of dollars worth of damage to economies worldwide.
Insects are among the most diverse and numerous life forms on earth. While the majority of the one million named species of insects are considered beneficial, somewhere from 1% to 5% are considered to be pests. Some of these insect pests not only cause tremendous losses in terms of direct destruction of crops, livestock, and human dwellings, they are also vectors for pathogens including protozoa, round worms, fungi, bacteria, and viruses that cause devastating human health problems. As climates change, with an overall tendency to warming, tropical and subtropical diseases are spreading into temperate regions, once devoid of these threats. The negative physical, mental, economic, social and ecological implications of disease carrying pest insects and arthropods are difficult to quantify since their effects are wide-ranging and multidimensional. As ecosystems in which humans dwell are harmed, water is polluted, sanitation hurdles mount, toxins are accumulated and food scarcity increases, animals (including humans) become much more susceptible to infection from pathogen-carrying insects and arthropods as their innate immune systems are weakened. Chemical pesticides, antibiotics, and vaccinations are notoriously ineffective against long-term exposure to populations of rapidly evolving organisms. Additionally, resistance to pesticides and antimicrobials can result in “super-bugs” which often develop in both insects and arthropods, as well as in the microbes they transmit. As diseases ebb and flow, we need a more sophisticated way of out-smarting the vectors that carry them. If the vector can be stopped, the disease can be stopped. By using attractants from entomopathogenic fungi, this new approach allows the unusual flexibility of being able to switch or combine attractant extracts and mycelium sourced by tapping into the vast and continually evolving genome of naturally occurring wild or human-improved strains.
Many insects and arthropods are vectors for contagions. Some in particular are common carriers of pathogens and contagions. Many of these contagions are spread by simple contact, some are spread from bites or proboscis punctures, while others can be transmitted to animals when they consume these disease-laden insects.
Zoonotic disease is defined as any disease that is spread from animals to people. The use of preconidial entomopathogenic fungi, and extracts and derivatives thereof, can also prevent non-zoonotic diseases, such as those transmitted to plants, including bacteria, fungi and viruses, which are also anticipated by the inventor. Any subsequent insect and arthropod controlling technology can be enhanced since the insects and arthropods become concentrated as a result of the attractant properties of the preconidial mycelium or extract of selected entomopathogenic fungi. A further novelty of this invention is that it allows other technologies that limit disease to work more effectively by concentrating and localizing the disease-spreading organism to a more centralized locus, reducing expenses while enhancing efficacies. In essence, disease vectors by insects and arthropods can be better controlled.
Mites and other arthropods can carry diverse populations of pathogenic bacteria, protozoa and viruses. For instance, ticks carry Borrelia species bacteria causing Lyme disease. In North America, Borrelia burgdorferi is a Gram-negative spirochete bacteria that is well known as the causative agent of Lyme disease. In Europe, Borrelia afzelii and Borrelia garinii are the bacteria known to transmit this disease. These bacteria, and likely more species yet to be discovered, spread to humans and animals by bites from ticks, especially species of ticks of the genus Ixodes. The western black-legged tick, Ixodes pacificus, in the western United States and the deer tick Ixodes scopularis (=Ixodes dammini) in the eastern United States are the primary species vectoring Borrelia bacteria to humans and other animals. Ticks in the genus Ixodes, such as I. scopularis, can also vector protozoa (from Babesiosis species), causing “Nantucket fever”, and some viruses, including encephalitis. More types of pathogens vectored by ticks are likely to be detected as research continues to track zoonotic and plant diseases.
Pharaoh Ants, Monomorium pharaonis and related species, are known as vectors to more than dozen pathogenic bacteria, including Salmonella spp., Staphylococcus spp., and Streptococcus spp., and are especially dangerous to burn victims recovering in hospital environments. See Beatson S. H., “Pharaoh ants as pathogen vectors in hospitals,” Lancet 1: pp. 425-427 (1972); Haack K. D., Granovsky T. A., Ants, In Handbook of Pest Control, Story K. and Moreland D. (eds.), Franzak & Foster Co., Cleveland, Ohio. pp. 415-479 (1990); and Smith E. H., Whitman R. C., Field Guide. Structural Pests, National Pest Management Association, Dunn Loring, Va., (1992).
Similarly, bed bugs can vector these same bacterial pathogens, endangering humans, typically while they sleep. Christopher F. Lowe and Marc G. Romney (Volume 17, Number 6—June 2011 in the Centers for Disease Control, Emerging Infectious Diseases, Letters, “Bedbugs as Vectors for Drug-Resistant Bacteria” reported that bed bugs vector methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) from bedbugs in Vancouver, British Columbia. Not surprisingly, the inventor anticipates many other bacterial, viral or protozoan diseases are likely to be discovered that are spread by these biting arthropods.
Below is a short summary of insects and arthropods with some of the zoonotic pathogens they transmit.
Arthropods Vectoring Zoonotic Pathogens
Bed Bugs: MRSA (methicillin resistant Staphylococcus aureus and Enterococcus faecium bacteria) carried by Cimex species; other bacteria.
Lice and ticks: Bacteria, including Rickettsia spp. causing Rocky Mountain Spotted fever; Bartonella vinsonii and B. henseiae causing intramuscular infections; and Borrelia burgdorferi, Borrelia afzelii and Borrelia garinii causing Lyme disease. Colorado tick fever, also called American mountain tick fever, is a viral infection transmitted from the bite of an infected Dermacentor andersoni tick. Powassan, a minor cause of viral encephalitis.
Mosquitoes: Malaria, Arboviral Encephalitides (viral diseases causing brain inflammation/encephalitis including West Nile virus, Japanese encephalitis, La Crosse encephalitis, St. Louis encephalitis, Eastern equine encephalitis and Western equine encephalitis), Dengue fever, Yellow fever, Rift Valley fever, dog heartworm.
Flies: Diseases carried by or transmitted by flies including typhoid, cholera, dysentery, infantile or summer diarrhea, pinkeye, salmonella, anthrax and tuberculosis. Tsetse flies transmit African trypanosomiasis (human sleeping sickness caused by Trypanosoma brucei). Sandflies transmit Chandipura virus.
Fleas: Bacteria, including Yersinia pestis causing bubonic plague, murine or endemic typhus, and Bartonella henselae, viruses including myxomatosis, reckettsial diseases, helminth (Hymenolepiasis tapeworm), trypanosome protozoa.
Triatomid bugs: Chagas disease (South American trypanosomiasis, Trypanosoma cruzi).
Midges: Viruses (Blue tongue virus to cattle, epizootic hemorrhagic disease).
Leafhoppers: Tomato/Tobacco Mosaic viruses, wheat striate mosaic virus, maize fine streak virus, chickpea chlorotic dwarf virus, green petal virus and others.
Virtually all biting insects and arthropods can result in bacterial or viral infections, either directly from a contagion reservoir within them or from wound exposure to the open environment. This is true with regard to both animal and plant diseases.
The present invention affords yet another new option for disease control: to attract but not necessarily kill arthropods, whilst reducing or eliminating their pathogen payloads. This option is important especially in areas where the arthropod populations are helpful in maintaining biological diversity of other animals that are dependent upon them for food. Removing all the arthropods from an ecosystem would likely result in unforeseen consequences, beyond that which is readily obvious. The food web is interconnected, and while most experts will agree that reducing disease vectors is prudent, destroying a native insect population is not.
Moreover, since Metarhizium and other entomopathogenic fungi are natural parasites of many arthropods, the natural genome of these fungal species offer sources of ever-evolving libraries of new strains, making resistance much more unlikely compared to chemical pesticides. An additional advantage of using preconidial entomopathogenic fungi such as Metarhizium anisopliae is that native strains of this fungus can be isolated wherever arthropods live, meaning that the constant co-evolution of this fungus to overcome resistance factors of the arthropods provides us with a unique partnership with nature to constantly adapt native, new strains of this fungus for implementation in controlling arthropods. Moreover, if new strains of Metarhizium anisopliae are blended with any antimicrobial or antiviral agent, the arthropods and the diseases they spread can be further controlled. Should the disease organism being carried by, for instance, a tick, develop resistance to an antimicrobial or antiviral drug, then a mixture of more than one drug or remedy can be employed to overcome resistance. Thus, this invention allows for a platform for continually out-evolving resistance by blending technologies and combining antimicrobials—out-racing the ability of arthropods and pathogens to adapt to either the entomopathogenic fungus or the antimicrobial method employed at the points of contact. Such synergism can have many derivative improvements and are expected by this inventor.
An example would be to blend the mycoattractive extracts and/or mycelia of preconidial entomopathogenic fungi attractive to arthropods with antiviral prodrugs, the less expensive antiviral drug precursors, expired antiviral drugs, or drugs such as Abacavir, Aciclovir, Acyclovir, Adefovir, Amantadine, Amprenavir, Ampligen, Arbidol, Atazanavir, Atripla, Boceprevir, Cidofovir, Combivir, Darunavir, Delavirdine, Didanosine, Docosanol, Edoxudine, Efavirenz, Emtricitabine, Enfuvirtide, Entecavir, Famciclovir, Fomivirsen, Fosamprenavir, Foscarnet, Fosfonet, Ganciclovir, Ibacitabine, Immunovir, Idoxuridine, Imiquimod, Indinavir, Inosine, Interferon type III, Interferon type II, Interferon type I, Interferon, Lamivudine, Lopinavir, Loviride, Maraviroc, Moroxydine, Methisazone, Nelfinavir, Nevirapine, Nexavir, Nucleoside analogues, Oseltamivir (Tamiflu), Peginterferon alfa-2a, Penciclovir, Peramivir, Pleconaril, Podophyllotoxin, Protease inhibitors, Raltegravir, Reverse transcriptase inhibitors, Ribavirin, Rimantadine, Ritonavir, Pyramidine, Saquinavir, Stavudine, Tea tree oil, Tenofovir, Tenofovir disoproxil, Tipranavir, Trifluridine, Trizivir, Tromantadine, Truvada, Valaciclovir (Valtrex®), Valganciclovir, Vicriviroc, Vidarabine, Viramidine, Zalcitabine, Zanamivir (Relenza®) and Zidovudine.
This same principle could also be used to enhance more traditional arthropod control devices. For example, blends of extracts and preconidial mycelium of entomopathogenic fungi can be used to enhance performance of bed bug control devices such as sticky mats, entanglements, piercers-and-hookers, blood or scent attractant based traps, darkened bed bug “hotel” collectors or wherever other “attract-and-trap” control mechanisms are installed. In essence, any current or future method might well result in greater performance for controlling arthropods, whether these be bed bugs, mites, ticks, mosquitoes or others, by employing extracts and mycelium of preconidial entomopathogenic fungi.
Because the purification of antimicrobial, antibacterial, antiprotozoal and antiviral drugs is typically more much expensive than their crude, or semi-pure precursors, this invention anticipates that less-than-pharmaceutical grade antimicrobial, antibacterial, antiprotozoal and antiviral medicines can be employed in combination with extracts and the mycelium of pre-conidial entomopathogenic fungi to create a successful treatment in the prevention, mitigation or curing of contagions transmitted by insects and arthropods. Moreover, the inventor's prior research on the use of polypore mushroom derivatives to combat viruses, which employ a similar method of extraction to the methods described herein for the creation of attractant preconidial entomopathogenic extracts, is yet another application of this novel way of limiting zoonotic and other forms and vectors of contagions.
Arthropods such as lice, bed bugs, mosquitoes, fleas and ticks can carry and transmit zoonotic diseases to humans and other animals, compounding the challenge faced by hospitals, hotels, homes, dormitories, army barracks, prisons and other densely populated areas. Denser populations of humans and animals—especially denser populations of immunocompromised humans and animals—increase the probably of infection and re-transmission.
Whether the initial infection being transmitted from a biting insect or arthropod is from a bacterium, a virus or a protozoan, co-occurrence of non-insect and non-arthropod borne diseases may more readily ensue. The now-lowered immunity of the infected animal population at large may, for instance, make the spread of Ebola, Hanta, bird flu viruses, diphtheria, dysentery, viral and bacterial meningitis or any contagion more readily spreadable. The resultant consequences of a population's lowered immunity can also degrade the overall population's immunological defenses against cancers. Conversely, those already suffering from cancer, or those with compromised immune systems due to other diseases, are more susceptible to infection.
Moreover, insects and arthropods spread viruses into plants. For instance, caterpillars and grasshoppers spread the Tomato-Tobacco Mosaic Virus. For farmers, there are dual advantages for controlling plant eating insects and the crop destroying diseases they spread. By combining extracts from the polypore mushroom, Fomes fomentarius, a source of antiviral agents active against the Tobacco Mosaic Virus with preconidial mycelium or extracts of Cordyceps species (well known for infecting caterpillars and grasshoppers), farmers could benefit by both limiting these crop damaging insects and lessening the threat of viruses they spread. This is but one of many examples that will become obvious and are expected manifestations of the current invention.
Hence this inventor sees a two-fold need: to control movement of insects and arthropods, and to control the pathogenic bio-burden of insects and arthropods that transmit diseases to people, animals, and plants. Combining methods and compositions discussed herein to create discrete ways to attract disease-carrying insects and subsequently killing them and/or reducing their pathogenic payloads will be important for protecting environmental health. In the age of technologies creating genetically modified organisms, potentiating pathogen carrying insects and arthropods as biological weapons is possible and protection from such threats is sorely needed. Hence, this invention could be important for defense against bioterrorism in its many elaborations.